1. Field of the Invention
The present invention relates to a system and method for spatially profiling a hydrophobicity distribution for a transmembrane protein, and more particularly, to a system for spatially profiling a hydrophobicity distribution for a transmembrane protein based on scaled hydrophobicity values for the transmembrane protein.
2. Description of the Related Art
The distribution of residue hydrophobicity from protein interior to exterior has been a subject of continued interest. The identification of the hydrophobic core of soluble globular proteins has provided a key feature relating an amino acid attribute to tertiary protein structure. Furthermore, a detailed relationship between the hydrophobic character of a local sequence of amino acids and variations of its proximity to the protein exterior has been described. The spatial segregation of residues, dependent upon amino acid hydrophobicity, has also assisted with validating predicted native protein structures, as well as with identifying the origin of nucleation sites during the initiation of protein folding.
While there has been a general consensus of opinion concerning the overall hydrophobic spatial distribution of the residues of soluble proteins, opinion concerning the hydrophobic distribution of the residues of transmembrane protein structures has had a more varied history. Early work had suggested that Bacteriorhodopsin was an “inside-out” protein. The terminology, “inside-out”, referred to a reversed sense of the hydrophobic distribution within the lipid bilayer from that of soluble globular proteins, namely, that the interior was composed of hydrophilic residues and the exterior of hydrophobic residues. Apparently the “inside-out” model of membrane protein structure is no longer accepted.
Notwithstanding, a relatively recent calculation that utilizes solvent-lipid accessibility, as have prior investigations, and purports to discredit the “inside-out” hypothesis, actually attempts to discredit a more general hypothesis, namely, that residues of greater hydrophobic character have a statistical preference to reside nearer the protein lipid interface. This latter hypothesis is independent of the residue character of the protein interior, being a statement of variations about the mean or average residue hydrophobicity of the distribution, whatever that distribution might be.
However, conventional systems and methods do not attempt to profile the distribution of hydrophobicity of transmembrane proteins. Thus, conventional systems and methods do not enable a determination of the spatial distribution of hydrophobicity within the interior of a structure, where the residue solvent-lipid exposure either vanishes or is minimal.